The soon-to-be-published next issue of the Journal of Clinical Oncology has another significant article coming out, this one reporting the results of a phase III trial looking at Rituxan maintenance in a specific population. It raises some interesting questions about the effectiveness of R maintenance -- more on that in a little bit.
The study focused on Follicular Lymphoma patients over 60 who had not received treatment. The researchers had two overarching goals -- the same goals that most researchers of FL treatments have: First, how can we find an effective treatment with less toxicity? Second, can we make the good results last longer than other treatments?
Their solution was to try a shorter course of R-FND (Rituxan, Fludarabine, Mitoxantrone, and Dexamethason), a not-uncommon treatment for older patients. (Fludarabine is fairly effective, but might get in the way of collecting stem cells later on, and can cause some secondary blood cancers years down the road -- less of a risk for older patients.) The patients received four monthly R-FND treatments, a less intense course than is typically given. These were followed up by a consolidation therapy (a second, different treatment given immediately after the first one, meant to catch any cancery leftovers): four weekly rounds of Rituxan.
This part of the study was fairly successful. Overall response was 86%, with 69% having a complete response. This answers that first question (how can we find an effective treatment with less toxicity?) with a big Yes.
Then came the second part of the study. The patients who remained in the study were divided into two groups: half were given Rituxan Maintenance (4 rounds, given every two months) and the other half were observed with no additional treatment. So, the answer to the second question (can we make the good results last longer than other treatments?) was a no. While the R-maintenance group had a 2-year Progression Free Survival of 81%, and the observation group's was 69%, this was not considered statistically significant (that is, there wasn't a big enough difference to say for sure that it was the Rituxan and not some other random factor).
On the surface, this would seem to be a blow for Rituxan maintenance. There was, after all, no real difference between the two groups.
However, two wicked smaht people from Dana-Farber in Boston wrote an accompanying editorial on the study called "One Size Does Not Fit All in Follicular Lymphoma." In their analysis of the study, R-maintenance isn't necessarily ineffective for FL. They point out that this is one of the few that does not show a benefit for R-maintenance. Another study, for example, tried R-maintenance with three groups -- some receiving R-CHOP, some R-CVP, and some R+another Fludarabine combo. The one that didn't get a maintenance benefit? The Fludarabine group. Their conclusion? Maybe R-maintenance doesn't work with some initial treatments (*cough-Fludarabine-cough*). They also point out that, given how effective Bendamustine is, with its much lower toxicity, maybe we just shouldn't bother with Fludarabine? Their final word: let's not assume Rituxan maintenance with work on everyone with Follicular Lymphoma; let's figure out which treatments it works best with first, and then use it with them.
I don't have much to add; the good folks from Boston did a fine job with their analysis. (Because, you know, they are cancer researchers at Dana-Farber, as opposed to me, who isn't.)
But it does provide some excellent food for thought when treatment decisions have to be made.